A Phase II Study of Pertuzumab and Erlotinib for Metastatic or Unresectable Neuroendocrine Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase II Study of Pertuzumab and Erlotinib for Metastatic or Unresectable Neuroendocrine Tumors (NCT00947167), a na phase 2 study. The primary outcome is Response Rate (RR) for All Patients Treated With This Strategy (Simon Design).

2. Clinical Question

3. Trial Design

This was a Phase II study of pertuzumab and erlotinib for metastatic or unresectable neuroendocrine tumors. It is recorded as a single-group, non-masked study, with allocation listed as not applicable. Enrollment was 4. The registry status is terminated; the record gives a start date of 2009-03 and a primary completion date of 2010-05.

The treatment strategy described in the registry began with pertuzumab alone. Erlotinib was to be added for participants whose disease was stable or progressive at three months. This is the planned sequence in the brief description, not a report of which participants actually received each treatment. The record does not describe individual treatment histories or explain why the study was terminated.

The primary objective was to determine objective response rates for all participants treated with the strategy, applying RECIST version 1.1. CT scans were scheduled every 4 cycles, described as every 12 weeks. A secondary outcome concerned toxicities assessed with CTCAE grading criteria and assigned attributions accordingly. The registry lists two outcome measures but does not provide numerical primary response results or detailed toxicity grades in the information recorded.

Because there was no separate comparator group, the design can describe outcomes among participants treated under the strategy but cannot make a direct treatment-versus-control comparison. The small enrollment also means that any observed count would represent a limited set of participants. The registry record does not report a fuller protocol, eligibility criteria, or reasons for termination.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Pertuzumab Alone

Erlotinib Added to Pertuzumab

Analysis population for the primary outcome, as defined in the registry: whole cohort

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Response Rate (RR) for All Patients Treated With This Strategy (Simon Design), measured over CT scans are done every 4 cycles (every 12 wks).

The primary endpoint was response rate for all participants treated with the strategy. The registry specifies that response was assessed using RECIST version 1.1. In general, an objective response endpoint classifies tumor response according to prespecified criteria, rather than relying only on a subjective impression. A response rate expresses how many participants in the defined analysis population met the response criteria.

The registry says the response rate was to be assessed for the whole cohort. That population definition matters: the endpoint was not described as applying only to participants who received erlotinib, or only to those who had stable or progressive disease after pertuzumab. The staged treatment strategy is part of the intervention being assessed.

The stated imaging schedule was CT scans every 4 cycles (every 12 weeks). Scheduled assessments help define when response is evaluated, but the registry record does not provide scan-level results, response classifications, or the numerical count meeting RECIST criteria. Therefore, the response endpoint’s meaning can be described, but its observed value cannot be interpreted from this record.

In general, response rate is useful for summarizing tumor response in a study, but it does not by itself describe every aspect of treatment experience or establish what would have happened under a comparator. Those broader conclusions require evidence and design features beyond a response count.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Clinical trial results depend on how outcomes are defined, who is included in the analysis, and how uncertainty is represented. The registry describes a Phase II, single-group study with a primary endpoint of response rate assessed using RECIST version 1.1. It does not report numerical response results or a statistical analysis result. The explanations below are general and clarify how such methods are ordinarily interpreted; they do not fill in details that are absent from the registry record.

What does a response rate represent?

In general, a response rate is a proportion based on a defined population: participants are classified according to whether they meet response criteria, and the number meeting those criteria is interpreted in relation to the population assessed. The registry identifies the whole cohort as the primary population. It also names RECIST version 1.1 as the response criteria. The numerical numerator and denominator used in an actual primary analysis are not reported in the registry record, so no response proportion can be reconstructed.

Response criteria make outcome classification more consistent by specifying how tumor measurements and changes are categorized. In general, consistent criteria can reduce ambiguity in interpreting imaging assessments. The registry says CT scans were scheduled every 4 cycles (every 12 weeks), but it does not report whether all planned scans occurred, how missing scans were handled, or whether response assessments were independently reviewed.

Why does the study design matter?

In a single-group study, outcomes are observed among participants receiving the study strategy, without a concurrent control group for direct comparison. This can describe what happened in the enrolled group, but a difference from an external expectation is not equivalent to a randomized treatment comparison. General factors such as participant characteristics, disease course, and assessment timing can influence observed outcomes. The registry’s allocation is listed as not applicable, and the study is explicitly single-group.

The planned strategy began with pertuzumab alone, with erlotinib added for participants with stable or progressive disease at three months. This makes the strategy a sequence rather than a fixed combination given to every participant from the outset. The registry does not report which participants reached the decision point, which treatment they received, or how those treatment histories were incorporated into an analysis. The stated primary population is all participants treated with the strategy.

How should uncertainty be understood?

In general, an estimate from a small group is imprecise because each participant’s outcome can have a substantial influence on the observed result. A confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. It does not guarantee that the underlying value lies within the interval, nor does it correct for bias or limitations in study design. No confidence interval for the response endpoint is reported in the registry record.

For event-count outcomes, the observed count and the population it represents should be kept distinct. A count is a direct record of events or participants meeting a definition; it is not by itself a precise estimate of event risk in a wider population. This distinction is especially important when enrollment is 4. The adverse-event counts are reported for the listed group, while event terms and further details are not reported.

What do the planning illustrations mean?

In general, a sample-size calculation asks how many participants might be needed under stated assumptions to detect a specified effect with a chosen statistical operating target. Such a calculation is a planning exercise, not an observed study result and not “observed power.” The registry’s accompanying planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect expressed as a stated fraction of the observed effect. Those assumptions do not match the recorded single-group trial design. They should therefore be understood as hypothetical planning conditions, not as the design actually used in this study.

When planning calculations are based on an observed effect, their outputs depend on that effect estimate and on the other assumptions. In general, a smaller target effect requires more information to detect than a larger target effect, all else held constant. This is a statistical principle, not a result about this trial. The registry record does not report a sample-size justification for the trial itself, and no planning illustration should be mistaken for the number enrolled, the number analyzed, or proof that the trial had adequate power.

What can be concluded from a p-value?

In general, a p-value describes how compatible data are with a specified statistical model and null hypothesis, under the analysis assumptions. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. No primary p-value or analysis result is reported in the registry record. Therefore, significance testing cannot be interpreted for the primary response endpoint from this record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Pertuzumab and Erlotinib")
n      <- c(4)
events <- c(0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Pertuzumab and Erlotinib  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary response-rate outcome and a secondary toxicity outcome. It does not report a multiplicity plan describing whether or how statistical error was controlled across outcomes, analyses, or subgroups. In general, evaluating many hypotheses can increase the chance of obtaining at least one apparently notable result by chance. Prespecified priorities and adjustment methods can help clarify how multiple results should be interpreted, but the registry record does not describe such methods.

The record lists two outcome measures and no analyses. It gives no numerical response result, and it does not report analysis populations beyond identifying the whole cohort for the primary endpoint. It is therefore not possible to determine from the registry record whether the primary analysis included every enrolled participant, how participants were classified if assessments were unavailable, or whether any participants were excluded from an analysis.

Missing-data handling is not reported in the registry record. In general, missing outcome assessments can affect an estimated response rate if participants without an assessment are treated differently from those with an assessment. Possible approaches depend on the outcome, timing, and prespecified analysis plan; none should be assumed for this study. The record also does not explain whether all scheduled CT scans were completed or how an incomplete assessment would have been categorized.

The registry’s two-sided significance level and equal-allocation assumptions appear in the planning illustration description, not as a reported analysis plan for this single-group trial. The record does not report interim analyses, a multiplicity adjustment, a sample-size justification for the trial, or a detailed statistical analysis plan. These absences limit assessment of how the endpoint was analyzed and how complete or robust any result might be.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

For the listed Pertuzumab and Erlotinib group, the registry reports 4 participants at risk for serious adverse events and 0 affected. For other adverse events, it reports 4 at risk and 4 affected. These are participant counts in the registry record, not event rates calculated for a broader population.

The serious-event count should not be read as proof that the strategy carries no serious-event risk. With enrollment of 4, the observed count represents a small group, and the registry record does not provide event terms, follow-up duration, or further participant-level detail. The record does not report deaths. The listed secondary outcome refers to toxicities assessed with CTCAE grading criteria and assigned attributions, but the grades and attribution details are not reported in the registry record.

“Other adverse events” should be kept distinct from serious adverse events. The registry records all 4 participants at risk as affected by other adverse events, but it does not specify the events or their severity in the information available. The counts do not indicate how many separate events occurred, when they occurred, or whether an event was considered related to a particular drug. The adverse-event figures are descriptive and do not provide a comparison with another group.

13. What the Result Does, and Does Not, Mean

The registry record establishes that this was a Phase II, single-group study of a staged pertuzumab and erlotinib strategy for metastatic or unresectable neuroendocrine tumors. It records enrollment of 4, a terminated status, a primary response endpoint using RECIST version 1.1, and CT imaging every 4 cycles (every 12 weeks). It also records selected adverse-event counts for the treatment group.

The primary response result itself is not reported in the registry record. No numerical response count or rate is available, so the treatment strategy’s observed response outcome cannot be characterized from this record. The missing result should not be interpreted as either no response or a particular level of response. Similarly, the study’s terminated status does not reveal why the trial ended or what its results were.

Even if a response count were available, the single-group design would limit causal interpretation. Without a control group, the study cannot directly establish how outcomes compare with another treatment or with no study treatment. The staged plan also leaves actual treatment receipt unclear: the registry describes when erlotinib was to be added but does not report which participants received it.

The adverse-event counts are limited descriptive information. The record reports 0 participants affected by serious adverse events and 4 affected by other adverse events, each among 4 at risk. These counts do not provide a complete safety profile, event descriptions, or evidence about comparative safety. No deaths are reported in the available record, but the deaths field is not populated with a numerical result.

In general, statistical evidence is best interpreted by considering the endpoint definition, the amount and completeness of data, uncertainty, and the design’s ability to support comparisons. Here, enrollment is small, key outcome details are absent, and there is no comparator. The appropriate reading is therefore limited to the information the registry records, without extrapolating to a broader population or treating the missing primary result as a finding.

14. Why This Trial Matters Statistically

This trial is statistically notable because its stated primary question and its design must be read together. The endpoint was response rate for the whole cohort, while the study was single-group and used a staged treatment strategy. Such a design can describe outcomes in the enrolled participants, but it does not create a direct treatment-versus-control contrast. Keeping those distinctions clear prevents a descriptive result from being interpreted as a comparative effect.

The record also illustrates why an endpoint definition is not the same as an endpoint result. It specifies RECIST version 1.1 and an imaging schedule of every 4 cycles (every 12 weeks), yet the numerical response outcome is not reported in the registry record. Readers can understand what investigators intended to measure without being able to assess the observed response or its precision.

Enrollment of 4 underscores the importance of uncertainty and the limits of generalization. General statistical reasoning indicates that a small cohort provides limited information for estimating outcomes beyond the participants observed. A count can be accurate as a record of those participants and still be uncertain as an estimate for a wider population. The registry does not report a response interval that would quantify that uncertainty.

Finally, the trial’s status and safety counts require restraint in interpretation. “Terminated” identifies the recorded status, not its reason. The recorded adverse-event counts describe events in the listed group, but they do not establish comparative safety or provide event-level detail. These features make the record useful for understanding study structure and reporting gaps, while limiting what can be concluded about outcomes.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most important trial-specific limitation in the registry record is the absence of the numerical primary response result. Although the objective response rate is identified as the primary outcome, the record does not state how many participants met RECIST version 1.1 response criteria or provide an estimated rate. No confidence interval or primary analysis result is reported.

Enrollment was 4, limiting the amount of outcome and safety information available. The single-group design has no control group, so it cannot support a direct comparison with another treatment or control condition. The staged strategy further complicates interpretation of exposure: pertuzumab was described as initial therapy, with erlotinib to be added for stable or progressive disease at three months, but actual treatment receipt is not reported.

The registry marks the study terminated but does not report the reason. It does not provide detailed eligibility criteria, participant characteristics, treatment duration, individual assessment histories, or the completeness of scheduled scans. It also does not describe how missing assessments were handled or identify the analysis population beyond the stated whole-cohort primary population.

Safety reporting is limited to participant counts. Event terms, grades, timing, attribution details, and deaths are not reported in the record. The listed toxicity outcome refers to CTCAE grading and attribution, but the detailed results needed to evaluate those measures are absent. These limitations mean that the recorded adverse-event counts should not be treated as a complete description of safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase II Study of Pertuzumab and Erlotinib for Metastatic or Unresectable Neuroendocrine Tumors — NCT00947167.
• Registry record last updated 2017-03-03; status last verified 2017-01.
• Results first posted 2017-03-03.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

This registry record describes a Phase II, single-group study of pertuzumab with possible later addition of erlotinib for metastatic or unresectable neuroendocrine tumors. It records enrollment of 4 and a terminated status. The primary endpoint was response rate for all participants treated with the strategy, assessed using RECIST version 1.1, with CT scans every 4 cycles (every 12 weeks).

The numerical primary response result is not reported in the registry record. The record reports 0 participants affected by serious adverse events among 4 at risk and 4 affected by other adverse events among 4 at risk. It does not report event-level details or a reason for termination. With no comparator group, the study’s design does not support a direct treatment comparison.